1. Field of the Invention
The invention relates generally compositions and methods for inducing bone growth or inhibiting bone loss and particularly to the use of isoflavones or metabolites thereof to induce bone growth or to inhibit bone loss.
2. Description of the Related Art
Bone remodeling is a continuing cycle. The cycle begins with osteoclast-mediated bone resorption and is followed by bone mass restoration by osteoblasts. The process of bone remodeling is primarily regulated by sex hormones, especially estrogen. However, genetic, nutritional, and environmental factors can influence bone turnover. Estrogen has been shown to plays a major role in bone remodeling in males as well as females. Estrogen reduces bone remodeling by suppressing osteoclastogenesis and osteoblastogenesis from marrow precursors, inhibits bone resorption by reducing pro-resorptive cytokines, and regulates the lifespan and activities of osteoblasts.
Dysregulation of the bone remodeling cycle often occurs. A more rapid rate of bone tissue dissolution and loss than bone tissue restoration is commonly observed among the aged population. Pathological bone loss is termed osteoporosis. Accelerated bone loss and osteoporosis disproportionately affects females. It is well accepted that estrogen deficiency, brought on by the onset of menopause in females, is a primary contributor to such bone loss. Nevertheless, bone loss and osteoporosis are observed in males.
Although there is no physiological equivalent to menopause in males, many males do experience an age-associated decrease in sex hormone circulation and hypogonadism. These changes are referred to as andropause. Hypogonadism and a decrease in estrogen contribute to bone loss and osteoporosis in males. Thus, both menopause and andropause are risk factors for bone loss.
In addition to menopause and andropause, surgical removal of sex organs affects the levels of sex hormones such as estrogen. Such removal can affect bone size, mass, and density. In animals, procedures such as neutering, spaying, ovariectomy, castration, and the like, are frequently performed for population control. The practical effect of a gonadectomy in mature female animals is the surgical equivalent of naturally occurring menopause in aged female animals because the procedure effectively diminishes circulating levels of sex hormones. After menopause, extragonadal biosynthesis of estrogen in female animals depends on the availability of precursor steroids from the adrenal cortex. Extragonadal biosynthesis of estrogen is also important for the normal function of many tissues and systems including bone in the male animals. Circulating testosterone from the testis appears to be the major precursor for extragonadal estrogen biosynthesis. Male animals maintain sufficient concentrations of circulating testosterone throughout life to support extragonadal biosynthesis of estrogen. Therefore, male animals usually do not suffer osteoporosis until very late in life. However, surgical removal of sex organs in mature male animals leads to complete loss of the production of androgen and estrogen by testis. Such removal also results in the loss of the major precursor for extragonadal estrogen biosynthesis that naturally does not occur in male animals.
Bone strength is largely dependent on bone density and bone quality. In humans, if peak bone mass is not reached in childhood and adolescence a risk of osteoporosis later in life arises. Surgical removal of sex organs in immature and growing male and female animals prevents the animals from reaching peak bone mass by reducing the accumulation of bone mineral density and content. As such, a gonadectomy can be considered a risk factor for impaired bone growth and development in young growing animals.
Hormone replacement therapy and dietary supplementation are frequently used to combat the effects of diminished sex hormone circulation on bone remodeling, particularly on bone loss. With respect to dietary supplementation, dietary phytoestrogens may improve bone mass and bone turnover and play a role in osteogenesis. In addition, dietary phytoestrogens are believed to have beneficial effects in slowing or inhibiting bone loss. However, almost all of the studies related to the beneficial effects of phytoestrogens such as soy isoflavones on bones were conducted in either female animals under the conditions of surgically-induced menopause or in postmenopausal women. There is a dearth of data regarding the effects of isoflavones on bone growth in growing animals and in male animals.
Phytoestrogens are chemicals produced by plants that have a similar structure to mammalian estrogens. Phytoestrogens are subdivided into three major classifications, i.e., coumestans, lignans, and isoflavones. The isoflavones have been shown to have positive effects on bone health.
Given the risk of (1) impaired bone growth and development and (2) accelerated bone loss and osteoporosis in animals that are in menopause or andropause or have been gonadectomized, especially when the animals are growing and their skeletal system has not matured yet, there is a need for novel compositions and methods that promote healthy bone growth and that reduce or inhibit bone loss in animals without the risk of dangerous side effects associated with traditional hormone replacement therapy.